Evidence has been obtained that adriamycin is capable of inducing the formation of single-strand regions in nuclear DNA. This drug induced response observed during the incubation of adriamycin with isolated nuclei will be examined in detail. Studies will be carried out to examine the strand separating activity of a variety of anthracycline analogs and other antitumor agents using nuclei and isolated chromatin structures. The nature and location of the single-strand regions in chromatin will be examined as well as the structural features and protein components of chromatin which are required for adriamycin to elicit the strand separating event. Studies will also be carried out to examine the strand separating activity of the anthracyclines using nuclei prepared from cells sensitive and resistant to adriamycin. The drug induced formation of single-strand regions will also be examined as a possible bioassay to screen for potential antitumor agents. Additional studies have demonstrated that upon incubation of adriamycin with isolated nuclei DNA strand breaks are introduced into nuclear DNA. The mechanism of DNA strand scission and the nature of the drug induced breaks formed in the in vitro system will be determined. Possible enzymes involved in the introduction of strand breaks in DNA complexed with adriamycin will be isolated and characterized. Experiments will also be carried out to examine the mode of action of a new anthraquinone derivative (DHAQ) which is showing considerable antitumor activity in experimental animals and is presently undergoing Phase I clinical trials.